The present invention relates to a method and apparatus for assessing the cardiovascular performance of a subject, particularly for diagnosing and/or monitoring treatment of patients with ischemic heart diseases (IHD) or with heart failure (HF).
Ischemic heart disease (IHD) is one of the major causes of morbidity and mortality in the developed countries. About 900,000 new patients of IHD are diagnosed every year in the USA. Many of these patients consequently suffer from reduced performance of the cardiovascular system (CVS) which deteriorates towards the clinical stage of heart failure (HF). Currently, about two milion patients have congestive HF in the USA; this number is expected to increase substantially. Patients with severe HF are limited in their daily life, are not capable of performing simple activities, and are hospitalized very often because of acute exacerbations of their disease. In addition to the sociologic impact of the disease, it has an enormous economical cost, including costs for expensive drug therapy, high rate of hospitalization costs, and loss of working days by the hospitalized or the medically-limited patients. About 35% of all patients with HF are hospitalized every year.
Large scale, multi-center therapy trials demonstrated that the mechanical performance of the heart is a major determinant of prognosis in HF patients and in patients with left-ventricular dysfunction after myocardial infarct. Other studies showed that the mechanical performance is an important determinant of functional capacity of these patients, although the interrelation between the two is more complex.
In addition to its role in prognosis assessment, the classification of HF severity is of importance in planning therapy. Drug therapy for HF patients is initiated with the following major goals: to relieve symptoms, to improve the quality of life, and to prolong life. Consequently, drugs are tested for their direct effect on functional capacity, e.g., by showing an improvement of exercise stress test performance, and by showing longer survival when compared with traditional therapy. However, large variations between individual subjects may modify their response to the standard drug therapy and result in a non-optimal effect. Thus the individual response to the therapy has to be monitored by follow-up evaluations, and appropriate adjustments in therapy may be required.
Unfortunately, current indices for non-invasive assessment of CVS mechanical performance, e.g., Ejection Fraction (EF), are inherently limited and may provide only weak correlations with functional capacity and quality of life. Nevertheless, the simplicity of non-invasive EF measurement makes it the most common index for the assessment of CVS performance.
A more accurate characterization can be based on a well established description of the CVS, which evolved from many years of physiological and pathophysiological research. The traditional framework is based on four main determinants of global CVS performance: myocardial contactility, ventricular preload, vascular load, and heart rate. For routine application in the clinical practice, these determinants have to be quantified by simple, non-invasive indices. An ideal index should be highly sensitive to the specific determinant and not sensitive to the other determinants. While indices for preload, afterload and heart rate are relatively easy to determine, a good index of myocardial contractility has been found to be more problemmatical.
The ventricular elastance, or end-systolic elastance (Ees), has been suggested as an index of myocardial contractility which is relatively independent on the other determinants. This index is physiologically related to the classical Frank-Starling Law, which constitutes the basis for the quantitative analysis of CVS performance. Since then, the index Ees was evaluated in numerous studies and became a well accepted index of myocardial contactility.
U.S. Pat. No. 4,877,035, which is hereby incorporated by reference, discloses a technique for determining the end-systolic elastance (Ees) of a subject's heart by measuring the end-systolic pressure-volume relation in which the afterload is varied by the controlled inflation of an intraaortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to transiently interrupt ventricular ejection at different times during the ejection phase, producing contraction at different ventricular volumes. Simultaneous measurements of left ventricular pressure and aortic volume during the occlusion sequence allows pressure vs. ejected volume loops to be generated, from which the slope of the end-systolic pressure-volume relationship can be determined.
The technique described in the above patent, however, is extremely limited in clinical practice because of the complex invasive procedure required, namely the introduction and controlled inflation of the intraaortic balloon.